The present research effort is directed at determining the relationship between diet and the etiology of colon cancer. It has been our objective to determine to what extent high fat and protein diets can alter the metabolic activity of the intestinal microflora. Previous studies in our laboratory have shown that meat-fed rats have higher activities of fecal bacterial enzymes capable of catalyzing the conversion of procarcinogens to carcinogens. In more recent studies we have shown that oral supplements of Lactobacillus acidophilus can lower fecal bacterial activity in humans and animals. Tetracycline and erythromycin, commonly used antibiotics, also lowered fecal bacterial enzyme activity in rats. A good correlation was attained when the enzyme data was compared with the incidence of colon tumors in rats receiving DMH. Meat-fed rats had a higher incidence of tumors. The incidence was lowered when animals were given antibiotics or Lactobacillus acidophilus. The reduction of orally administered nitronaphthalene was also tested as a function of diet. Meat-fed rats had more naphthylamine in their feces after being orally given nitronaphthalene, demonstrating that the elevated nitroreductase levels resulting from the diet can affect procarcinogen formation. A higher level of naphthylamine was also measured in the feces of meat-fed animals given naphthylamine-beta-D-glucuronide. This again demonstrates the importance of fecal enzyme levels, in the case beta-glucuronidase. Oral supplements of L. acidiphilus also decreased the conversion of nitronaphthalene or naphthylamine-beta-D-glucuronide to naphthylamine in the meat-fed rats. In a similar type study women were given either tetracycline or ampicillin and the amount of ethenyl estradiol (EE2) excreted in urine and feces were measured. Three of four women who normally excreted a significant amount of EE2 in the urine had increased fecal extraction of EE2 in the feces after antibiotic treatment. This again indicates the importance of the fecal flora in hydrolytic reactions which can lead to the generation of carcinogens in the bowel.